PI3Kα/CDK7-IN-1
PI3Kα/CDK7-IN-1 is a dual-target hybrid inhibitor of PI3Kα and CDK7, with IC50 values of 87.9 nM and 638 nM, respectively. PI3Kα/CDK7-IN-1 acts as a cytotoxic agent and cell death inducer that triggers apoptotic death in cancer cells. PI3Kα/CDK7-IN-1 can be used in cancer research such as colorectal cancer.
For research use only. We do not sell to patients.
- Formula: C26H25F3N9O3PS
- Molecular Weight:631.57
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
PI3Kα 87.9 nM (IC50) |
CDK7 638 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HCT-116 | IC50 |
360 nM
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Cytotoxicity against human HCT116 cancer cells (carrying activating PI3Kα driver mutation) assessed as reduction in cell viability via 10-point titration for IC50 determination.
Cytotoxicity against human HCT116 cancer cells (carrying activating PI3Kα driver mutation) assessed as reduction in cell viability via 10-point titration for IC50 determination.
|
42468711 |
| SK-OV-3 | IC50 |
490 nM
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Cytotoxicity against human SKOV3 cancer cells (carrying activating PI3Kα driver mutation) assessed as reduction in cell viability via 10-point titration for IC50 determination.
Cytotoxicity against human SKOV3 cancer cells (carrying activating PI3Kα driver mutation) assessed as reduction in cell viability via 10-point titration for IC50 determination.
|
42468711 |
| MCF7 | IC50 |
820 nM
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Cytotoxicity against human MCF7 cancer cells (carrying activating PI3Kα driver mutation) assessed as reduction in cell viability via 10-point titration for IC50 determination.
Cytotoxicity against human MCF7 cancer cells (carrying activating PI3Kα driver mutation) assessed as reduction in cell viability via 10-point titration for IC50 determination.
|
42468711 |
In Vitro
PI3Kα/CDK7-IN-1 (Compound HY5) inhibits the viability of HCT116, SKOV3 and MCF7 cancer cells carrying PI3Kα mutations, with IC50 values of 360 nM, 490 nM and 820 nM, respectively[1].
PI3Kα/CDK7-IN-1 reduces the viability of MDA-MB-231, U2OS and NCI-H522 cancer cells, and exhibits stronger activity against NCI-H522 cells overexpressing SLC7A11[1].
PI3Kα/CDK7-IN-1 (10 μM; 48 h) alters cell cycle progression, induces apoptosis and non-apoptotic cell death, and triggers cellular stress responses in HCT116 cells, as evidenced by increased phosphorylation levels of CDK/MAPK substrates, reduced mitotic index, upregulated levels of activated caspase-3, and formation of pyknotic nuclei[1].
PI3Kα/CDK7-IN-1 (10 μM; 48 h) induces cellular stress responses in HCT116 cells[1].
PI3Kα/CDK7-IN-1 (5-10 μM; 24-48 h) reduces the viability of HCT116 cells through both caspase-dependent apoptotic and non-apoptotic mechanisms[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:HCT116 colon cancer cells
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Concentration:10 μM
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Incubation Time:48 h
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Result:Increased global phosphorylation of CDK and MAPK substrates.
Caused a ~2-fold increase in DAPI staining intensity.
Reduced the mitotic index to undetectable levels.
Induced a slight but significant decrease in RB phosphorylation at serine 780.
Increased cleaved caspase-3-positive cells to 17% compared to vehicle-treated cells.
Chemical Information
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Molecular Weight 631.57
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Formula C26H25F3N9O3PS
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SMILES
FC(F)(C(C=NC(NC1=C(N=C(NC(N(CCC2)C2C(N)=O)=O)S1)C)=N3)=C3C4=CNC5=C4C=CC(C#N)=C5P(C)(C)=O)F
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)